Lactol PAF antagonists

Abstract

PCT No. PCT/GB91/00596 Sec. 371 Date Oct. 23, 1992 Sec. 102(e) Date Oct. 23, 1992 PCT Filed Apr. 16, 1991 PCT Pub. No. WO91/17157 PCT Pub. Date Nov. 14, 1991.The invention encompasses compounds of general formula I: <IMAGE> (I) wherein W represents an imidazo[4,5-c]pyridyl group, optionally substituted with one or more substituents selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CF, and CN; and Z, R1, R2, R3, R4, R5, R6 are variables. These compounds are useful as antagonists of platelet activating factor.

We claim: 
     
       1. A compound of general formula I: ##STR61## wherein: W represents an imidazo[4,5-c]pyridyl group, optionally substituted with one or more substituents selected from C 1  -C 6  alkyl, C 1  -C 6  alkoxy, halo, CF, and CN; Z represents a divalent alkanediyl group from 2 to 8 carbon atoms which may be a straight or branched-chain having at least 3 carbon atoms in the chain linking W to the oxygen atom;   R 1  represents a V group wherein V is a ##STR62##  group wherein t is zero and each of R 9 , R 10  and R 11  is independently hydrogen, C 1  -C 6  alkyl, C 1  -C 6  alkoxy, C 1  -C 6  alkylthio, halo, CN, NO 2 , SOC 1  -C 6  alkyl, SO 2  C 1  -C 6  alkyl, SO 2  (CH 2 ) 1-4  CH 2  OH, SO 2  NH 2 , CO 2  H, CO 2  C 1  -C 6   alkyl, CHO, COC 1  -C 6  alkyl, CH 2  OH, OH, benzyl, benzoyl, CF 3 , CONH 2 , NHCOC 1  -C 6  alkyl, or an NR 15  R 16  group wherein each of R 15  and R 16  is independently hydrogen or C 1  -C 6  alkyl; and   each of R 2 , R 3 , R 4 , R 5 , and R 6  represents hydrogen; or a pharmaceutically or veterinarily acceptable acid addition salt or hydrate thereof.     
     
     
       2. A compound according to claim 1 wherein W represents a 1H-2-methylimidazo[4,5-c]pyridyl group. 
     
     
       3. A compound according to claim 1 wherein the grouping W--Z--O-- and the substituent R 1  are in the cis configuration with respect to the lactone ring. 
     
     
       4. A compound according to claim 1 wherein the grouping W--Z--O-- and the substituent R 1  are in the trans configuration with respect to the lactone ring. 
     
     
       5. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(3,4-dimethoxyphenyl)-gamma-butyrolactol ether. 
     
     
       6. A compound according to claim 1 which is O-(4-(1H-2-methylimidazo[4,5c]pyridyl)butyl)-5-(3,4-dimethoxyphenyl)-gamma-butyrolactol butyrolactol ether. 
     
     
       7. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-gamma-butyrolactol ether. 
     
     
       8. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(4-fluorophenyl)-gamma-butyrolactol ether. 
     
     
       9. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(4-bromophenyl)-gamma-butyrolactol ether. 
     
     
       10. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(3,4-dichlorophenyl)-gamma-butyrolactol ether. 
     
     
       11. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(3-chloro-4-methoxyphenyl)-gamma-butyrolactol ether. 
     
     
       12. A compound according to claim 1 which is O-(3-(1H-2-methylimidazo[4,5-c]pyridyl)propyl)-5-(3,4,5-trimethoxyphenyl)-gamma-butyrolactol ether.